Microfluidic impedance cytometry enables label-free and real-time single-cell analysis by detecting changes in electrical impedance as cells traverse microchannels. Electrode configuration plays a critical role in determining detection sensitivity, signal quality, and spatial resolution. In this study, finite element simulations were conducted to model the impedance response of mammalian red blood cells under various electrode designs, including coplanar, parallel, tilted, and parabolic configurations, as well as electrode layouts coupled with flow velocity. A multiphysics simulation model is established to analyze the effects of geometric parameters on electric field distribution and impedance response. The results demonstrate that optimized electrode arrangements significantly enhance detection performance and enable multi-parameter analysis. Furthermore, the influence of flow dynamics and dielectric properties on impedance signals is explored. These findings provide both theoretical and experimental guidance for the development of high-efficiency, integrated impedance cytometry platforms, contributing to the advancement of microfluidic systems in biomedical diagnostics and single-cell characterization.